1. Field of the Invention
The present invention relates to methods of ameliorating damage caused by ischemia in myocardial tissue and other tissues.
2. Description of the Prior Art
Depletion of purine nucleotide pools is postulated to play a role in cardiac and skeletal muscle dysfunction. A decrease in the total amount of adenine nucleotides and especially adenosine triphosphate (ATP) results from the insufficient energy supply available during low oxygen levels. Various methods have been proposed to protect the myocardium during anaerobic situations, both those resulting from disease or injury, such as myocardial infarctions and those deliberately induced, such as induced cardiac arrest without coronary perfusion for cardiac surgery. One of the methods intended to improve myocardial anoxic tolerance and to improve and accelerate post-anaerobic recovery is the administration of adenosine, as described in, for example Isselhard et al., Journal of Molecular and Cellular Cardiology, 12, 619-634 (1980). However, the various purine precursors, such as adenosine, inosine, and hypoxanthine which have previously been used to restore ATP levels have deleterious hemodynamic effects on the cardiovascular system. This is particularly true of adenosine which is known to have significant effects on heart rate, systemic blood pressure, cardiac output, and regional myocardial blood flow. Accordingly, new agents and methods of using them which provide the desired increase in the adenine nucleotide pool without deleterious effects on the cardiovascular system are needed.